Injection cartridges have found a wide use for administering injectable pharmaceutical preparations by means of injection or infusion. Such cartridges have a number of important advantages over the use of syringes filled before use from a separate vial, such as their ease of handling and the lessened risk of microbial contamination. An injection cartridge generally comprises a tubular barrel, which contains a liquid injectable preparation. At its front end, the barrel is sealed by a closure, which may be pierced by an outlet conduit, such as an injection needle or cannula or a tube for infusion. At its rear end, the cartridge is closed by a piston, which may be moved forward to expel the injectable preparation from the cartridge through the outlet conduit. This type of injection cartridge is known as a single-chamber injection cartridge.
Dual-chamber injection cartridges are also well-known. Such cartridges are intended to be used for injectable preparations which are not stable in their ready-to-use state, and the space between the front closure and the rear piston is divided into two chambers, which are separated by a separating movable wall. The front chamber usually contains a solid component of the injectable preparation, and the rear chamber contains a liquid component of said preparation. At a predetermined position in the cartridge, there is arranged a longitudinally extending liquid bypass arrangement in the wall of the cartridge, such that the liquid component may bypass the movable separating wall and flow into the front chamber to be mixed with the solid component. When a forwardly directed pressure is applied to the rear piston, this pressure will be translated through the liquid to urge the movable wall forward. When the movable wall has moved far enough towards the front chamber such that the inlet of the bypass arrangement is open to the rear chamber, further forward movement of the rear piston will cause the liquid from the rear chamber to flow through said bypass arrangement and mix with the component in the front chamber. In this way, the two components may be mixed with each other just before the injection is to be administered, and there will be no time for degradation of the ready-mixed preparation. Once all the liquid has been transferred from the rear chamber to the front chamber, further movement of the rear piston will cause it to abut the movable separating wall, and with continued movement forward rear piston and movable separating wall will act as a single piston for expelling the mixed preparation from the cartridge.
U.S. Pat. No. 4,439,184 discloses a two-dose syringe with a dual chamber, intended to provide two separate bodies of fluid in a sequence. As a first body of fluid is pushed out of the syringe a first piston, made of resilient material, reaches a bypass zone having at least one ridge projecting into the fluid chamber from its wall. This ridge pushes the first piston away from the wall so that the fluid between the first and second pistons can pass around the first piston to an output zone.
A dual-chamber injection cartridge is disclosed in WO 94/01150. It has a front chamber for a solid component and a rear chamber for a liquid component. The injection cartridge further comprises a bypass constriction with a non-circular cross-section for allowing the flow of liquid from the rear chamber into the front chamber when a front piston of resilient material is urged into the constriction by the movement of a rear piston.
As indicated, known in the art are multiple chamber cartridges comprising a) a barrel having a front face comprising an outlet (or preparation for an outlet), b) a movable front piston in the barrel which defines a front chamber between the front piston and the front face of the barrel c) a movable rear piston defining a rear chamber between the rear piston and the front piston d) a rear bypass allowing fluid transfer from the rear chamber to the front chamber and e) a front bypass allowing fluid transfer past (or through) the front piston to the outlet.
Antihaemophilic preparations are normally stored and distributed in lyophilized form, reconstituted before administration and injected via a needle or tube with cannula. When the administration of a liquid preparation from an injection cartridge has been finished and the rear piston is in its foremost position, there exists a dead volume of unusable preparation in front of the piston in the front end part of the cartridge and in the outlet of the cartridge. This dead volume can be considerable, especially when a tube of some length is arranged between the outlet and the needle or cannula. This is a disadvantage, as it means that a certain amount of the pharmaceutical preparation will not be utilized by the patient. The disadvantage is aggravated when very expensive pharmaceutical preparations are used, such as growth hormones and certain peptides.
Various ways have been tried to eliminate this disadvantage. One way has been to draw some blood back into the cartridge after the finished injection and then inject it back into the patient, so that the outlet is rinsed in this way. This practice, however, is not to be recommended, as there is a risk that the components of the blood, which are very sensitive to surfaces, will be destroyed or will coagulate to form clots. Another way has been to remove the syringe containing the pharmaceutical agent and replace it with a syringe containing a rinsing liquid, such as physiological saline solution, to finish the injection. This is complicated and time-consuming, and increases the risk of spillage and contamination.
There are known cartridges having a third chamber which is arranged to allow for both mixing of two components into a mixture before ejection, as well as ejection of a rinsing liquid following the ejection of the mixture, resulting in a two-step sequential ejection pattern.
EP 0 721 357 discloses a three-chamber injection cartridge containing a front chamber with a solid preparation component, an intermediate chamber with a liquid component, a rear chamber with a rinsing liquid and rear and front bypasses for reconstitution and sequential ejection respectively. This injection cartridge could offer a solution to the disadvantage of dead volumes when administering pharmaceutical preparations. There are however very few manufacturing plants in the world that manufacture injection cartridges pre-filled with lyophilized products and all of these lack process stations for charging a third chamber and a third piston. Hence there is a need for a user-friendly and efficient injection cartridge enabling the full use of valuable pharmaceutical preparations.